Digitalisation and diabetes technology have become decisive factors in modern diagnostics and treatment for diabetes mellitus, which especially involves the development and use of decision support systems such as KADIS (R). This contribution presents five selective programmes based on KADIS (R) with retrospective evaluation alongside cost coverage: DIABETIVA (R), DiabetesSpeziat KADIS (1), Ther@Optimum Diabetes, and KADIS (2).All five programmes saw a reduction in mean HbA(1c) values where medical practices and patients implemented personal metabolic optimisation recommendations based on KADIS (R). Q-Scores also decreased. Acceptance and satisfaction with telemedical consultation and decision support were found to be high amongst patients and physicians, with baseline HbA(1c) values playing a major role in the DIABETIVA (R) programme. Decision support systems also yielded economic benefits.

Fragestellung: Neben dem Langzeitparameter HbA1c steht mit der Glukosevariabilität ein Beurteilungsparameter der kurzfristigen Stoffwechseleinstellung des Patienten zur Verfügung. Mit DIABETIVA® bot die ehemalige Taunus BKK im Rahmen eines IV-Vertrages einen Beitrag zur Diabetestherapieoptimierung an. Unter Nutzung von Selbstkontrolldaten und kontinuierlichem 72-Stunden Glukosemonitoring (CGM) können mit dem Beratungssystem KADIS® Therapieoptionen in-silico entsprechend den DDG-Leitlinien simuliert und die abgeleiteten, individuellen Empfehlungen dem behandelnden Arzt zur Verfügung gestellt werden.

Continuous subcutaneous insulin infusion (CSII) has become a standard for treatment optimization of type 1 diabetes (T1D). However, the transition from Multiple DoseInjection (MDI) to CSII therapy can be challenging. The objective of the present study was to use KADIS, the Karlsburg Diabetes Management System, for individual basal and bolus insulin adjustments in patients with type 1 diabetes while switching from MDI to pump therapy. We describe the extended KADIS-CSII program and its practical application for adjustment of insulin pump therapy. We conducted a pilot study including 12 patients with T1D who had received MDI therapy consisting of short- and long-acting insulin injections. Baseline HbA1c was 8.2±0.8 %, age 31.3±11.1 years, and diabetes duration 15.7±6.7 years (mean±SD). Data derived from continuous glucose monitoring (CGM) during MDI therapy were processed by the KADIS algorithm in order to characterise the patient’s specific metabolic parameters. Those were used to estimate individual basal infusion rate patterns as well as insulin boluses based on carbohydrate consumption for the transition to CSII. Three months after transitioning from MDI to CSII based on KADIS guided therapy, the mean HbA1c value was reduced to 7.6±0.5 % (–0.6 % vs. baseline, p<0.05) and remained at this level until the end of the 6-month study. Likewise, time <3.9 mmol/L (p=0.008), glycemic variability indexes, such as SD around mean glucose (p=0.010), MAGE (p=0.001), and CONGA (p=0.007), were all significantly lower at study end. Consistent with these data, quality of glycemia measured by the GRADE index and a recently developed Q-score was also improved. The proposed KADIS-CSII program could become a practicable and efficient toolto support adjusting insulin pump therapy.

Diabetes mellitus is a chronic disease that through its complications seriously reduces quality of life and life expectancy in diseased people. There is a worldwide increase in the prevalence in diabetes mellitus type 2. Our understanding in reducing the micro- and macrovascular risk has increased in the last time. But, in contrast to microvascular morbidity the most persistent menace to the health in diabetic patients of both types remains atherosclerosis with increased cardiovascular morbidity and mortality when compared with the non-diabetic population. In the past, the role of hyperglycemia on CVD was not completely elucidated. It was the aim to review and to compare the role of hyperglycemia on cardiovascular morbidity and mortality both in type 2 and type 1 diabetes. Results from ADVANCE and UKPDS Studies in type 2 diabetes have shown that the effect of intensive glucose control was associated with decreased risk of cardiovascular disease and death from any cause in addition to reduction of microvascular disease. HbA1c targets lower than 7.5 % and near to 6.5 % and avoiding of hypoglycemia are recommended. DCCT-EDIC Study data in type 1 diabetes have demonstrated that an early intensive metabolic control near to normal level initiated in patients with short diabetes duration and without microangiopathic complications such as nephropathy significantly reduced micro- and macrovascular morbidity. The long lasting effect of intensive control is called «memory effect». Near normal HbA1c levels at least < 7.5 % and individually targeted in order to avoid hypoglycemia are required. When comparing both types of diabetes, in type 1 as well as type 2 diabetes intensified glucose control resulted in long-lasting effects, reducing significantly cardiovascular morbidity and mortality. Treatment has to be initiated early in the course of the disease. But considering meta-analyses of large randomized controlled trials of intensive vs. conventional glycemiccontrol in type 2 diabetes, hyperglycemia has shown to be a weaker cardiovascular risk factor than increased cholesterol levels or hypertension.

An important advantage of pump therapy (CSII) is that it can adjust basal insulin dose to the individual needs of diabetic patients using short-acting insulin only. In addition, delayed insulin bolus release gradually adapts to carbohydrate absorption after a meal with bolus size calculated according to insulin release history and current blood glucose readings. CSII especially requires basal rate settings to match the patient's individual profile, involving a time-consuming procedure for diabetes teams that constitutes an additional burden on the patient. KADIS (R)-CSII software specifically developed for the purpose provides an effective alternative. KADIS (R)-CSII continuously records glucose profiles in configuring and optimising CSII within minutes. A feasibility study tested the software on twelve type 1 diabetes patients; adjustment took less than half an hour after analysis. KADIS (R)-CSII initiated individual adaptations from the standard profiles commonly used, adaptations that would have otherwise required procedures such as meal omission tests. HbA(1c) levels decreased from 8.2 +/- 0.8% to 76 +/- 0.5% (p<0.051 after three months, and remained at this level. KADIS (R)-CSII thus contributes towards effective, convenient and rapid CSII configuration.

Fragestellung: Ziel der retrospektiven Auswertung war die Untersuchung des Einflusses der Anwendung des interaktiven Beratungssystems KADIS® auf die Stoffwechselgüte bei Patienten in der klinischen Routine im Verlauf von 2 Jahren.

Fragestellung: In der Auswertung des DIABETIVA®-Programm wurde untersucht, ob die Anwendung des Expertensystem KADIS® einen Einfluss auf die Glukosevariabilität von Blutzuckertagesprofilen (BZP) als Indikator zur Beurteilung der Stoffwechsellage bei Diabetikern hat.

Aims: Die Inkretine GIP (gastric inhibitory polypeptide) und GLP-1 (glucagon-like-peptide-1) stimulieren die Insulinsekretion unter Hyperglykämie. Nach wie vor werden die insulinotropen Effekte von GIP und/oder GLP-1 bei Typ 2 Diabetikern kontrovers diskutiert. Wir entwickelten ein experimentelles Testmodell, um die Dosis-abhängige Insulin-Antwort nach GLP-1 and GIP Injektion unter vergleichbaren Bedingungen messen zu können. In vorangegangenen Untersuchungen an normoglykämischen Wistar Ratten konnten wir belegen, dass 2 nmol/kg GIP and 4 nmol/kg GLP-1 über eine vergleichbare insulinotrope Potenz verfügen. Es zeigte sich aber, dass eine DPP-4 Hemmung den Glukosetoleranz verbessernden und insulinotropen Effekt von GIP verstärkt, denjenigen von GLP-1 jedoch signifikant reduziert. Dieser unerwartete Befund sollte nun in einem Typ 2 diabetischen Modell hinsichtlich seiner Relevanz geprüft werden.

Aims: In our preceding study DPP-4 inhibition diminished GLP-1 incretin effects. This finding sheds new light on biological role of GLP-1 metabolite (GLP-1m). In the present study we investigated the involvement of GLP-1m in the effects exerted by GLP-1 incretin and the time duration through which GLP-1m effects are maintained.

Fragestellung: Inkretinanaloga sind eine neue Klasse Glukose senkender Wirkstoffe, die die Eigenschaft besitzen, die glykämischen Stoffwechselprozesse vergleichbar den natürlichen Inkretinen zu beeinflussen. Exenatide ist das erste zugelassene Inkretinanaloga, welches die Insulinsekretion fördert, die postprandiale Glukagonsekretion hemmt und die Nahrungsresorption verzögert. Erste therapeutische Anwendungen von Exenatide haben aber auch gezeigt, dass die erwarteten therapeutische Effekte bei einigen Probanden voll zum Tragen kommen bei anderen aber nicht. Gegenwärtig existiert aber keine Methode, mit welcher der zu erwartende therapeutische Effekt bereits vor der Applikation abgeschätzt werden könnte. Es war daher das Ziel dieser Studie, eine Methode zu entwickeln und zu verifizieren, die es erlaubt, Low- oder High-Responder einer Inkretintherapie zu identifizieren.

Aims: Studies in man and pig have shown that GLP-1 (9–36) amide (GLP-1m) is a glucoregulatory peptide, but its insulinotropic actions are not yet fully investigated.

The model-based Karlsburg Diabetes Management System (KADIS®) has been developed as a patient-focused decision-support tool to provide evidence-based advice for physicians in their daily efforts to optimize metabolic control in diabetes care of their patients on an individualized basis. For this purpose, KADIS® was established in terms of a personalized, interactive in silico simulation procedure, implemented into a problem-related diabetes health care network and evaluated under different conditions by conducting open-label mono- and polycentric trials, and a case–control study, and last but not least, by application in routine diabetes outpatient care. The trial outcomes clearly show that the recommendations provided to the physicians by KADIS® lead to significant improvement of metabolic control. This model-based decision-support system provides an excellent tool to effectively guide physicians in personalized decision-making to achieve optimal metabolic control for their patients.

Aims: DPP-4 (dipeptidyl peptidase-4) inhibition has been reported to increase incretin effects of GIP as well as GLP-1 by prolonging their half life. DPP-4 cleaves GIP into dipeptide and the GIP metabolite GIP (3–42), whereas the GLP-1 (7–36) amide is cleaved to GLP-1 (9–36) amide. Based on studies in man, pig and rat, these peptides are involved in various glucoregulatory processes. We have recently developed a test to differentiate the insulinotropic effects of both peptides in rats. In the present study, we compared the insulinotropic effects of the intact GIP and the GLP-1 (7–36) amide during IVGTT following DPP4 inhibitor administration.

Increased IMT is an important surrogate parameter for increased cardiovascular morbidity. In continuation of previous studies, it was the aim of present cross-sectional study to evaluate the relationship of IMT with cardiovascular risk and morbidity in a cohort of 310 well characterized type1 diabetic patients. According to IMT, patients were divided into tertiles: <= 0.06 (group0, 120patients): 0.05 +/- 0.08; 0.065-0.075 (groupI, 83patients): 0.069 +/- 0.029; >= 0.08 (groupII, 107patients): 0.094 +/- 0.036. The study population had a mean age of 50.7years, diabetes duration of 23.8years, HbA1c of 8.38%, and BMI of 27.2kg/cm(2). Among the 107patients of groupII 62patients were of male sex (57.9 %, p<0.01). These patients were characterized by a mean age of 60.6 years (p<0.01), mean diabetes duration of 29.6 years (p<0.01), mean age of disease manifestation of 30.9years (p<0.01), BMI of 28.3 (p<0.01), mean waist circumference of 101.9cm (p<0.01), mean systolic BP of 127mmHg (p<0.01), mean diastolic BP of 71mmHg (p<0.01). There were increased prevalences of hypertension (92.5%, p<0.01), smoking history (27.4%, p<0.05), proliferative retinopathy (28.2%, p<0.01), maculopathy (19.0%, p<0.05), diabetic foot syndrome (7.5%, p<0.05), diabetic neuropathy (52.9%, p<0.01), hyperlipo-proteinemia (77.4 %, p<0.01), coronary artery disease (30.3 %, p<0.01), and peripheral vascular disease (33.6%, p<0.01). As shown by univariate correlation analysis (Spearman' Rho) IMT was significantly related to age, diabetes duration, age of diabetes manifestation, bodyweight, BMI, waist circumference, serum creatinine and systolic blood pressure ( for all p<0.01). In multiple logistic regression analysis IMT was independently associated with male sex (OR 3.0, p<0.01), age (OR 1.2, p<0.01), waist circumference (OR 1.05, p<0.05), smoking history (OR 4.7, p<0.01), peripheral arterial disease (OR 4.1, p<0.01), and neuropathy (OR 0.12, p<0.01). In type1 diabetes, increased IMT was found to be associated with cardiovascular risk as indicated by both increased concentrations of classic and modifiable atherosclerosis risk factors, and cardiovascular morbidity.

Serum activities of complement-dependent antibody mediated cytotoxicity (C'AMC) were determined in 36 consecutive patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). The sequential exposure of 51Cr labeled neonatal rat islet cells to patient serum and rabbit complement revealed the presence of C'AMC in 28 IDDM subjects. The C'AMC titres ranged between 1:4 and 1:512 and were not related to the C'AMC activity of a given sample as measured at a standard dilution (1:4). In comparison to the clinical characteristics of 21 IDDM patients with negative C'AMC, higher C'AMC titres (greater than or equal to 1:32) were associated with a lower mean age at diagnosis of IDDM (12.2 +/- 2.1 vs. 19.0 +/- 2.3 years; p less than 0.05), with a higher frequency of infections up to 6 months prior to diagnosis (6 out of 11 vs. 3 out of 21 patients; p less than 0.05) and, although statistically not significant, a preponderance of female sex together with a decreased frequency of HLA-DR4. In contrast, fasting C-peptides levels, HLA-DR3 antigen frequency and Coxsackie B1-6 virus antibody titres were not related to the C'AMC titres. It is concluded that (1) C'AMC titration is superior to the detection of initial C'AMC levels for evaluating the strength of the complement-dependent humoral immune response towards islet cell surface (auto)antigen(s), and (2) infectious agents may be involved in eliciting a C'AMC response.

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.

Given the importance of glucose variability in the development of diabetic complications, the present study used continuous glucose monitoring (CGM) to determine various indices of glucose variability and to investigate their relationships with conventional measures of chronic sustained hyperglycemia. We examined 53 women and 61 men, aged 36-79 years afflicted with type 2 diabetes for 1-24 years. The following indices of glycemic variability were computed from CGM data sets: mean amplitude of glycemic excursions (MAGE), CGM glucose range, interquartile range (IQR), SD-score, and average daily risk range (ADRR). CGM measurements and self-monitored blood glucose (SMBG) records were used to calculate mean CGM sensor glucose and mean SMBG, respectively. In simple correlation analysis, the indices of glucose variability showed weak correlations with HbA1c: MAGE (r=0.27, p <0.01), CGM glucose range (r=0.21, p <0.05), IQR (r=0.31, p <0.01), SD-score (r=0.34, p<0.001), and ADRR (r=0.24, p<0.05). These indices were found to differ at identical HbA1c among several patients, as reflected by diurnal excursions of different frequency and magnitude. With the exception of ADRR, stronger correlations were found between mean SMBG and the other variability indices (r=0.51-0.63, p<0.01 for all). CGM provides various indices of glycemic variability not captured by conventional measures of glycemic control. Detection of the location and the magnitude of glucose fluctuations by CGM should aid in optimal treatment of glycemic disorders in type 2 diabetes.

A sensitive and versatile radioimmunoassay (RIA) for insulin was established using human insulin standard, a specific guinea pig anti-insulin antiserum and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations were used for as long as 6 weeks after iodination. The standard curve ranges from 0.044 to 1.2 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.4 and 0.9 nmol/l. The average recovery of human insulin added to plasma or serum samples was 100.2 +/- 2.0% (n = 38) and 100.1 +/- 1.9% (n = 42), respectively. In addition to human insulin, porcine, canine, rabbit and bovine insulin can also be determined but not rat or mouse insulin. The cross-reactivity of the antiserum with porcine proinsulin was found to be 40% on the molar basis. The range of mean fasting plasma insulin concentrations in healthy subjects and under various pathological conditions were estimated.